This report describes a statewide study conducted to develop main-channel slope (MCS) curves for 138 selected streams in Iowa with drainage areas greater than 100 square miles. MCS values determined from the curves can be used in regression equations for estimating floodfrequency discharges. Multivariable regression equations previously developed for two of the three hydrologic regions defined for Iowa require the measurement of MCS. Main-channel slope is a difficult measurement to obtain for large streams using 1:24,000-scale topographic maps. The curves developed in this report provide a simplified method for determining MCS values for sites located along large streams in Iowa within hydrologic Regions 2 and 3. The curves were developed using MCS values quantified for 2,058 selected sites along 138 selected streams in Iowa. A geographic information system (GIS) technique and 1:24,000-scale topographic data were used to quantify MCS values for the stream sites. The sites were selected at about 5-mile intervals along the streams. River miles were quantified for each stream site using a GIS program. Data points for river-mile and MCS values were plotted and a best-fit curve was developed for each stream. An adjustment was applied to all 138 curves to compensate for differences in MCS values between manual measurements and GIS quantifications. The multivariable equations for Regions 2 and 3 were developed using manual measurements of MCS. A comparison of manual measurements and GIS quantifications of MCS indicates that manual measurements typically produce greater values of MCS compared to GIS quantifications. Median differences between manual measurements and GIS quantifications of MCS are 14.8 and 17.7 percent for Regions 2 and 3, respectively. Comparisons of percentage differences between flood-frequency discharges calculated using MCS values of manual measurements and GIS quantifications indicate that use of GIS values of MCS for Region 3 substantially underestimate flood discharges. Mean and median percentage differences for 2- to 500-year recurrence- interval flood discharges ranged from 5.0 to 5.3 and 4.3 to 4.5 percent, respectively, for Region 2 and ranged from 18.3 to 27.1 and 12.3 to 17.3 percent for Region 3. The MCS curves developed from GIS quantifications were adjusted by 14.8 percent for streams located in Region 2 and by 17.7 percent for streams located in Region 3. Comparisons of percentage differences between flood discharges calculated using MCS values of manual measurements and adjusted-GIS quantifications for Regions 2 and 3 indicate that the flood-discharge estimates are comparable. For Region 2, mean percentage differences for 2- to 500-year recurrence- interval flood discharges ranged between 0.6 and 0.8 percent and median differences were 0.0 percent. For Region 3, mean and median differences ranged between 5.4 to 8.4 and 0.0 to 0.3 percent, respectively. A list of selected stream sites presented with each curve provides information about the sites including river miles, drainage areas, the location of U.S. Geological Survey streamflowgaging stations, and the location of streams crossing hydrologic region boundaries or the Des Moines Lobe landform region boundary. Two examples are presented for determining river-mile and MCS values, and two techniques are presented for computing flood-frequency discharges.